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Table of Contents

Table of Contents

Abstract
01. Abstract
Presentation
01. Introduction02. Patient Features at Baseline03. Diffusion MRI Processing04. Voxelwise Mean Diffusivity Analysis05. Regional Diffusivity Measures06. Sample Size Analysis07. Summary

Given that the FTD variants have a complex overlapping set of clinical and anatomical phenotypes, identifying disease specific regions and minimizing the number of participants with disease subtypes in clinical trials is critical. An aim of this work was to identify the brain regions that require the lowest sample sizes to detect potential therapeutic effects for FTD clinical trials.

t-stat map of 12 month change from baseline in mean diffusivity for the bvFTD variant

By using both the exploratory voxelwise analysis and regional diffusivity metrics, we have shown:

  • The spatial & temporal complexity associated with brain structural changes in the FTD variants.
  • The distinct frontal (bvFTD) versus temporal (svPPA) patterns of change in mean diffusivity between the FTD varaints.
  • The brain regions that require the lowest sample sizes to detect potential therapeutic effects for FTD clinical trials.
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This work provides a detailed analysis of diffusion MRI data from the FTLDNI  study. Our results show that progressive, regional microstructural changes can be effectively assessed using quantitative analysis of diffusion MRI data with reasonable sample sizes over a relatively short timeframe. As such, these imaging biomarkers appear to be promising for assessment of the efficacy of disease-modifying therapeutics in FTD clinical trials.

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